| 1 | 摩尔。Psychiatry 2003 Feb 8: 148-55 |
|---|---|
| PMID | 12610647 |
| 标题 | The axonal chemorepellant semaphorin 3A is increased in the cerebellum in schizophrenia and may contribute to its synaptic pathology. |
| 抽象的 | The neuropathological features ofschizophrenia联想是一个发育印第安纳州吗uced impairment of synaptic connectivity. Semaphorin 3A (sema3a) might contribute to this process because it is a secreted chemorepellant which regulates axonal guidance. We have investigatedsema3ain the cerebellum (an area in which expression persists in adulthood), and measured its abundance in 16 patients withschizophreniaand 16 controls. In adults,sema3awas predominantly localized to the inner part of the molecular layer neuropil, whereas infants and rats showed greater labelling of Purkinje cell bodies.sema3a增加了schizophrenia, as shown by enzyme-linked immunosorbent assay (+28%; P<0.05) and immunohistochemistry (+45%; P<0.01). We also measured reelin mRNA, since reelin is involved in related developmental processes and is decreased in other brain regions inschizophrenia. Reelin mRNA showed a trend reduction in the subjects withschizophrenia(-26%; P=0.07) and, notably, was negatively correlated withsema3a.sema3a也与突触素和复杂蛋白II mRNA负相关。结果表明sema3ais elevated inschizophrenia, and is associated with downregulation of genes involved in synaptic formation and maintenance. In this respect,sema3aappears to contribute to the synaptic pathology ofschizophrenia, perhaps via ongoing effects of persistentsema3aelevation on synaptic plasticity. The findings are consistent with an early neurodevelopmental origin for the disorder, and the reciprocal changes insema3aand reelin may be indicative of a pathogenic mechanism that affects the balance between trophic and inhibitory factors regulating synaptogenesis. |
| SCZ关键字 | 精神分裂症，精神分裂症 |
| 2 | 摩尔。精神病学2008年7月13日：673-84 |
| PMID | 17684500 |
| 标题 | 复制在第7q22染色体上的连锁和区域reelin基因与精神分裂症家族中工作记忆的关联。 |
| 抽象的 | schizophrenia是一种常见且复杂的精神障碍。遗传因素对其病因很重要，但是尽管向不同人群中的几个染色体区域报告了连锁信号，但对诱发基因的最终鉴定仍然是一个挑战。利用大型家庭schizophrenia来自芬兰的研究样本，我们已经确定了几个链接的基因座：1q32.2-Q42、2Q，4Q31、5Q和7Q22。在这项研究中，一个独立的352个核样本schizophrenia家族（n = 1626）允许在7q21-32上复制连锁。在与揭示了四个区域候选基因的连锁，SNP和微卫星关联分析的245个核科（n = 1074）样本中sema3aand VGF, revealed no significant association to the clinical diagnosis ofschizophrenia. Instead, quantifiable trait component analyses with neuropsychological endophenotypes available from 186 nuclear families (n=861) of the sample showed significant association to RELN variants for traits related to verbal (P=0.000003) and visual working memory (P=0.002), memory (P=0.002) and executive functioning (P=0.002). Trait-associated allele-positive subjects scored lower in the tests measuring working memory (P=0.0004-0.0000000004), memory (P=0.02-0.0001) and executive functioning (P=0.001). Our findings suggest that allelic variants of RELN contribute to the endophenotypes ofschizophrenia. |
| SCZ关键字 | 精神分裂症，精神分裂症 |
| 3 | Schizophr. Res. 2008 Feb 99: 56-70 |
| PMID | 18248790 |
| 标题 | Maternal infection leads to abnormal gene regulation and brain atrophy in mouse offspring: implications for genesis of neurodevelopmental disorders. |
| 抽象的 | 产前病毒感染与schizophreniaand autism. Our laboratory has previously shown that viral infection causes deleterious effects on brain structure and function in mouse offspring following late first trimester (E9) administration of influenza virus. We hypothesized that late second trimester infection (E18) in mice may lead to a different pattern of brain gene expression and structural defects in the developing offspring. C57BL6J mice were infected on E18 with a sublethal dose of human influenza virus or sham-infected using vehicle solution. Male offsping of the infected mice were collected at P0, P14, P35 and P56, their brains removed and prefrontal cortex, hippocampus and cerebellum dissected and flash frozen. Microarray, qRT-PCR, DTI and MRI scanning, western blotting and neurochemical analysis were performed to detect differences in gene expression and brain atrophy. Expression of several genes associated withschizophreniaor autism includingsema3a, Trfr2 and Vldlr were found to be altered as were protein levels of Foxp2. E18 infection of C57BL6J mice with a sublethal dose of human influenza virus led to significant gene alterations in frontal, hippocampal and cerebellar cortices of developing mouse progeny. Brain imaging revealed significant atrophy in several brain areas and white matter thinning in corpus callosum. Finally, neurochemical analysis revealed significantly altered levels of serotonin (P14, P35), 5-Hydroxyindoleacetic acid (P14) and taurine (P35). We propose that maternal infection in mouse provides an heuristic animal model for studying the environmental contributions to genesis ofschizophrenia和自闭症，这是神经发育障碍的两个重要例子。 |
| SCZ关键字 | 精神分裂症，精神分裂症 |
| 4 | Psychiatry Res 2015 Oct 229: 850-7 |
| PMID | 26243375 |
| 标题 | 在具有听觉幻觉和没有听觉的精神分裂症患者的前额叶皮层中，词素和丛蛋白基因表达改变了。 |
| 抽象的 | Auditory hallucinations (AH) are clinical hallmarks ofschizophrenia，无论这些症状的分子遗传学知之甚少。在这项研究中，来自前额叶皮层的尸体后脑样品的基因表达分析schizophrenicpatients without AH (SNA), patients with AH (SA) and control subjects were compared. Genome-wide expression analysis was conducted using samples of three individuals of each group and the Affymetrix GeneChip Human-Gene 1.0 ST-Array. This analysis identified the Axon Guidance pathway as one of the most differentially expressed network among SNA, SA and CNT. To confirm the transcriptome results, mRNA level quantification of seventeen genes involved in this pathway was performed in a larger sample. PLXNB1,sema3a与对照组相比，SNA或SA患者的SEMA4D和SEM6C在SNA或SA患者中被上调。PLXNA1和SEMA3D在患者的样品中表达下调，但SNA患者和对照组之间的差异在统计学上显着。在SA患者的PLXNB1表达中发现了SNA和SA之间的差异。这项研究加强了大脑可塑性在病理生理学的贡献schizophrenia并表明，与关于神经可塑性的幻觉相比，非六位化患者在额叶区域的改变更多。 |
| SCZ关键字 | 精神分裂症，精神分裂症 |
| 5 | Psychiatry Res 2015 Oct 229: 850-7 |
| PMID | 26243375 |
| 标题 | 在具有听觉幻觉和没有听觉的精神分裂症患者的前额叶皮层中，词素和丛蛋白基因表达改变了。 |
| 抽象的 | Auditory hallucinations (AH) are clinical hallmarks ofschizophrenia，无论这些症状的分子遗传学知之甚少。在这项研究中，来自前额叶皮层的尸体后脑样品的基因表达分析schizophrenicpatients without AH (SNA), patients with AH (SA) and control subjects were compared. Genome-wide expression analysis was conducted using samples of three individuals of each group and the Affymetrix GeneChip Human-Gene 1.0 ST-Array. This analysis identified the Axon Guidance pathway as one of the most differentially expressed network among SNA, SA and CNT. To confirm the transcriptome results, mRNA level quantification of seventeen genes involved in this pathway was performed in a larger sample. PLXNB1,sema3a与对照组相比，SNA或SA患者的SEMA4D和SEM6C在SNA或SA患者中被上调。PLXNA1和SEMA3D在患者的样品中表达下调，但SNA患者和对照组之间的差异在统计学上显着。在SA患者的PLXNB1表达中发现了SNA和SA之间的差异。这项研究加强了大脑可塑性在病理生理学的贡献schizophrenia并表明，与关于神经可塑性的幻觉相比，非六位化患者在额叶区域的改变更多。 |
| SCZ关键字 | 精神分裂症，精神分裂症 |